We are studying the levels of proinsulin in the blood and urine of normal subjects and patients with islet cell tumors and diabetes mellitus. In addition, we are investigating the effect of pregnancy on circulating values. The C-peptide immunoassay has been applied to the diagnosis of hypoglycemic disorders to follow the natural history of beta cell function in insulin requiring diabetic patients. We are attempting to correlate the ease of control in individual patients with their capacity to secrete C-peptide (insulin). The metabolism of C-peptide and proinsulin is under investigation in man. The relative contributions of the liver and kidney to their total metabolic clearance are being assessed. Bibliographic references: Alsever, R.N., Roberts, J.P., Gerber, J.G., Mako, M.E. Rubenstein, A.H. Insulinoma with low circulating insulin levels: The diagnostic value of proinsulin measurements. Ann. Int. Med. 82: 347-350 (1975), Constan, L., Mako, M., Juhn, D., and Rubenstein, A.H. The excretion of proinsulin and insulin in urine. Diabetologia 11: 119-123 (1975).